The basal forebrain cholinergic system is the predominant source of cortical cholinergic input and is comprised of cholinergic projection neurons travelling from the basal telencephalon through the neocortex to the hippocampus, olfactory system, cortical mantle, and amygdala. Alzheimer's disease-related tauopathies arise earliest in cholinergic neurons of the basal forebrain and loss of these neurons parallels cognitive decline (1-4). Human lesion (5-7) and MRI (8) studies have demonstrated the role of BFCN in memory function, while studies in monkeys, rats and mice using a specific BFCN immunotoxin have further demonstrated the role of these cells in memory function (9-12), hippocampal neurogenesis, and the survival of new neurons (13-15). Additionally, numerous animal models have demonstrated the necessity of BFCN for functional plasticity of the motor cortex after training (16) or damage (17), and also throughout the visual (18) and auditory (19) cortices, data which can be partially replicated with anticholinergic drugs in humans (20). Being of such import in Alzheimer's disease, memory formation, and cortical plasticity, the derivation of BFCN from human stem cells could be of great potential therapeutic benefit as it might allow the repopulation of BFCN after loss or damage.